CARCINOGENS UNDER THE SCAN

As trace amounts of cancer-causing contaminants continue to crop up in certain medicines, pharma companies are upgrading their testing methods and equipment to meet increased regulatory scrutiny. The result? Safer medicines but even thinner margins

- Viveka Roychowdhury

It is now one and a half years since the carcinogenic contaminant N-nitrosodimethylamine (NDMA) was first detected in sartans in June 2018. The fact that high blood pressure medicines are prescribed for long time use, on a daily basis added to the risk that life long use of NDMA, even in trace amounts, was definitely more harmful than the occasional exposure to the carcinogen from certain food and environmental sources.

While global regulators alerted companies and distributors, pharma companies withdrew their stocks from circulation. Once tests confirmed the presence, batches were recalled. The presence was found to be an impurity in API supplied by a Chinese API manufacturer, Zhejiang Huahai and linked to a change in the process of synthesis.

It was almost action replay in September 2019, when trace amounts of NDMA were found in rantidine, an anti-ulcerant, commonly prescribed and available as OTC brands as well. Unlike sartans, ranitidine is not prescribed for long term use. And unlike sartans, the contaminant is not part of the medicine but thought to have been formed during the testing process, when the high temperature required for gas chromatography-mass spectrometry (GC-MS) caused ranitidine to react with itself and form nitrosamines.

Though the US online pharmacy Valisure which detected this felt that there was evidence to suggest NDMA formation under these conditions in the human body, the US FDA did not believe this was the case. The agency said that GC-MS was the suggested testing procedure for nitrosamine impurities in sartans, not in ranitidine. For the latter, the US FDA prescribed an alternative liquid chromatography-high resolution mass spectrometry (LC-HRMS) method, which showed much lower levels of nitrosamine impurities than Valisure. NDMA and N-nitrosodiethylamine (NDEA) have also been found in pioglitazone, used to treat type 2 diabetes mellitus.

The aftermath